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临床试验/NCT05392556
NCT05392556已完成不适用

Prebiotic and Probiotic Modulation of the Gut Microbiota-gut-brain Axis During Acute Stress

United States Army Research Institute of Environmental Medicine2 个研究点 分布在 1 个国家目标入组 73 人开始时间: 2022年7月6日最近更新:
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适应症

试验速览

阶段
不适用
状态
已完成
发起方
入组人数
73
试验地点
2
主要终点
Change from baseline in intestinal permeability
研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Emerging evidence supports the existence of a microbiota-gut-brain axis through which gut microbes influence cognition, mood and behavior. Targeting this axis with probiotics and/or prebiotics may provide novel strategies for mitigating stress-induced decrements in gastrointestinal and cognitive function. This double-blind, placebo-controlled, randomized, parallel-arm trial will determine the effects of a prebiotic and a probiotic dietary intervention on gastrointestinal, cognitive and physiologic responses to acute military-relevant physical and cognitive stress. Healthy men and women will be recruited and randomized to receive a placebo, probiotic or prebiotic for 4wk. Volunteers will be fed a controlled diet during the 4th week of supplementation. Fecal, blood, urine and saliva samples will be collected. Physical stress will be induced by a weighted walk on a treadmill, and will be followed by a cognitively challenging testing scenario that uses intermittent electric shocks to the abdomen to induce a stress response.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Other
盲法
Triple (Participant, Investigator, Outcomes Assessor)

盲法说明

Participants, study investigators, and study staff will be blinded to the intervention. A staff member not involved in the study will randomize the participants and inform the Principal Investigator of the randomization order upon enrollment of each participant.

入排标准

年龄范围
17 Years 至 39 Years（Child, Adult）
性别
All
接受健康志愿者
是

入选标准

  • •Men and women aged 18 - 39 years (active duty personnel who are 17 yr of age will also be allowed to participate).
  • •In good health as determined by Medical Clearance.
  • •Physically active:
  • •If military, passed most recent record Combat or Physical Fitness Test, and ≥4 d/wk aerobic and/or resistance exercise.
  • •If civilian, ≥4 d/wk aerobic and/or resistance exercise.
  • •Meet Army weight for height and body composition standards as defined in Army Regulation 600-9:
  • •Self-reports ≥4 bowel movements/week.
  • •Self-reports normal hearing.
  • •Willing to maintain usual diet until provided diet phase of study.

排除标准

  • •Pregnant, expecting to become pregnant during study, or breastfeeding.
  • •Abnormal menstrual cycles [i.e., not between 26-32 days in duration; or not 5-6 menstrual cycles within the past 6 months], or those that have had an IUD placed within the last month or removed within the past 3 months.
  • •Less than 20/20 acuity on the Snellen eye chart of normal or corrected-to-normal acuity.
  • •Any of the following medical conditions:
  • •Neurological or psychological disorder (such as depression, anxiety disorders, migraines, cluster headaches, seizures, post-traumatic stress disorder or panic attacks).
  • •Cardiac disease (including arrhythmia or fast or skipped heart beats) Hypertension Has a pacemaker Insomnia Musculoskeletal injuries that compromise exercise capability Metabolic or cardiovascular abnormalities (e.g., kidney disease, diabetes, etc.) Disease of the GI tract including, but not limited to diverticulitis, inflammatory bowel disease, irritable bowel syndrome, peptic ulcer disease, Crohn's disease, and ulcerative colitis Excessive alcohol use or other substance abuse issues Immunodeficiency disorder Allergy to skin adhesive
  • •Colonoscopy within 3 months of study participation.
  • •Any use of antibiotics or antimycotics, except topical antibiotics/antimycotics, within 3 months of study participation.
  • •Regular use of over-the-counter medications (including antacids, laxatives, stool softeners, and anti-diarrheals) unless approved by medical office and study PI.
  • •Taking prescription medications other than a contraceptive (unless approved by medical office and study PI)
  • •Not willing or able to refrain from using over the counter medications for 72hr before stress exposure days.
  • •Not willing or able to stop consumption of dietary supplements at least 2 weeks before and throughout study participation.
  • •Not willing or able to stop consumption of probiotic-containing foods (e.g., yogurt, etc.) or foods containing added prebiotics (e.g., inulin) at least 2 weeks before and throughout study participation.
  • •Not willing to abstain from non-provided foods and beverages, including alcohol, during the controlled-diet period.
  • •Not willing to abstain from caffeine and any nicotine containing products (smoking, chewing, vaping, etc.) during the week prior to stress exposure days.
  • •Not willing to refrain from strenuous exercise for 24hr prior to stress exposure days.
  • •Allergies, intolerances, unwillingness or inability to eat intervention supplements, or provided foods and beverages.
  • •Following vegetarian/vegan diet or other highly restrictive diet (e.g., ketogenic diet, very high protein diet, Paleo diet).
  • •Any previous blood donation, within 8 weeks of a study blood draw, of a volume that when combined with the amount of blood to be collected during the study would exceed 550 mL

结局指标

主要结局

Change from baseline in intestinal permeability

时间窗: Days 0 and 29

A differential sugar absorption test will be used to assess intestinal permeability. Participants will consume 2g sucralose and 4g mannitol dissolved in 180 mL water prior to starting exercise. Participants will then collect all urine produced over the subsequent 4hr. Urine sucralose and mannitol concentrations will be analyzed.

Difference from baseline in circulating cortisol concentrations

时间窗: Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.

Serum cortisol concentrations will be measured in serial blood samples collected via an indwelling venous catheter.

次要结局

  • Difference from baseline in circulating norepinephrine concentrations(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.)
  • Difference from baseline in circulating neuropeptide Y concentrations(Before (-20min) exercise and immediately before cognitive stress exposure on days 0 and 29)
  • Difference from baseline in circulating brain-derived neurotrophic factor (BDNF) concentrations(Before (-20min) exercise and immediately before cognitive stress exposure on days 0 and 29)
  • Difference from baseline in circulating S100 calcium binding protein B (S100B) concentrations(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.)
  • Difference from baseline in circulating lipopolysaccharide concentrations(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.)
  • Difference from baseline in circulating zonulin concentrations(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.)
  • Difference from baseline in circulating intestinal fatty acid binding protein (I-FABP) concentrations.(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.)
  • Difference from baseline in fecal acetate concentrations(Pre-intervention, week 3 and week 4)
  • Difference from baseline in fecal propionate concentrations(Pre-intervention, week 3 and week 4)
  • Difference from baseline in fecal butyrate concentrations(Pre-intervention, week 3 and week 4)
  • Difference from baseline in gut microbiota composition(Pre-intervention, week 3 and week 4)
  • Change from baseline in salivary secretory immunoglobulin A(Day 0 and Day 29)
  • Difference from baseline in salivary cortisol concentrations(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29)
  • Change from baseline in mean heart rate variability(During stress exposure (up to 4hr) on days 0 and 29.)
  • Change from baseline in performance on decision making under conditions of ambiguity task(Days 0 and 29)
  • Difference from baseline in reaction time.(Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.)
  • Difference from baseline in response inhibition(Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.)
  • Difference from baseline in working memory(Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.)
  • Difference from baseline in circulating epinephrine concentrations(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.)
  • Difference from baseline in distractibility to emotional stimuli(Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.)
  • Difference from baseline in emotional states measured by the Depression, Anxiety and Stress Scale (DASS)(Day 0, Week 1, Week 2, Week 3, Day 29)
  • Difference from baseline in mood state measured by the Profile of Mood States 2-A (POMS2A)(Before (-45min) and immediately after exercise, and after cognitive stress exposure on days 0 and 29)
  • Difference from baseline in feelings of pleasantness(Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.)
  • Difference from baseline in feelings of arousal(Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.)
  • Difference from baseline in gastrointestinal discomfort(Day 0, Week 1, Week 2, Week 3, Day 29)
  • Difference from baseline in gastrointestinal symptoms(Day 0, Week 1, Week 2, Week 3, Day 29)
  • Difference from baseline in circulating cytokines concentrations.(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29)
  • Difference from baseline in circulating dehydroepiandrosterone-sulfate (DHEA-S) concentrations(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29)
  • Change from baseline in mean heart rate variability(During stress exposure (up to 4hr) on days 0 and 29.)
  • Change from baseline in performance on decision making under conditions of ambiguity task(Days 0 and 29)
  • Difference from baseline in response inhibition(Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.)
  • Difference from baseline in reaction time.(Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.)
  • Difference from baseline in working memory(Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.)
  • Difference from baseline in emotional states measured by the Depression, Anxiety and Stress Scale (DASS)(Day 0, Week 1, Week 2, Week 3, Day 29)
  • Difference from baseline in distractibility to emotional stimuli(Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.)
  • Difference from baseline in mood state measured by the Profile of Mood States 2-A (POMS2A)(Before (-45min) and immediately after exercise, and after cognitive stress exposure on days 0 and 29)
  • Difference from baseline in feelings of pleasantness(Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.)
  • Difference from baseline in feelings of arousal(Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.)
  • Difference from baseline in gastrointestinal discomfort(Day 0, Week 1, Week 2, Week 3, Day 29)
  • Difference from baseline in gastrointestinal symptoms(Day 0, Week 1, Week 2, Week 3, Day 29)
  • Difference from baseline in circulating cytokines concentrations.(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29)
  • Difference from baseline in circulating dehydroepiandrosterone-sulfate (DHEA-S) concentrations(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29)
  • Difference from baseline in circulating epinephrine concentrations(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.)
  • Difference from baseline in circulating norepinephrine concentrations(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.)
  • Difference from baseline in circulating neuropeptide Y concentrations(Before (-20min) exercise and immediately before cognitive stress exposure on days 0 and 29)
  • Difference from baseline in circulating brain-derived neurotrophic factor (BDNF) concentrations(Before (-20min) exercise and immediately before cognitive stress exposure on days 0 and 29)
  • Difference from baseline in circulating S100 calcium binding protein B (S100B) concentrations(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.)
  • Difference from baseline in circulating lipopolysaccharide concentrations(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.)
  • Difference from baseline in circulating zonulin concentrations(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.)
  • Difference from baseline in circulating intestinal fatty acid binding protein (I-FABP) concentrations.(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.)
  • Difference from baseline in fecal acetate concentrations(Pre-intervention, week 3 and week 4)
  • Difference from baseline in fecal propionate concentrations(Pre-intervention, week 3 and week 4)
  • Difference from baseline in fecal butyrate concentrations(Pre-intervention, week 3 and week 4)
  • Difference from baseline in gut microbiota composition(Pre-intervention, week 3 and week 4)
  • Change from baseline in salivary secretory immunoglobulin A(Day 0 and Day 29)
  • Difference from baseline in salivary cortisol concentrations(Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29)

研究者

发起方
United States Army Research Institute of Environmental Medicine
申办方类型
Fed
责任方
Sponsor

研究点 (2)

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